Terpene Synthases and Cytochrome P450s: Partners in Plant Diterpene Diversity

Terpenes constitute the largest and most diverse class of plant specialized metabolites, mediating physiological processes throughout the plant life cycle. Among these, diterpenes (C20) serve as precursors for hormones (gibberellins), components of electron transfer chains, and accessory pigments. Beyond their endogenous roles, diterpenes, including carnosol, tanshinones, paclitaxel, ingenol mebutate, sclareol, and andrographolides, possess pharmacological activities. Diterpene diversity is initiated by the cyclization of geranylgeranyl pyrophosphate (GGPP) by terpene synthases (TPSs), followed by scaffold tailoring primarily mediated by cytochrome P450 monooxygenases (CYPs). Intriguingly, genes encoding TPS-CYPs enzymatic duo are frequently found in genomic proximity, either as pairs or within biosynthetic gene clusters (BGCs). This co-localization is driven by whole-genome duplications (WGD), tandem rearrangements, and neofunctionalization to facilitate the coordinated transcriptional regulation. In this review, we provide an in-depth overview of the evolution, genomic organization, and biochemical signatures of TPS-CYP pairs from lower plants, gymnosperms, and angiosperms, and the following part covers the chromatin-level regulatory mechanisms that mediate their expression. By bridging evolutionary history with modern genomic arrangements, this review offers a unified perspective on how TPS-CYP partnerships drive the vast chemical landscape of plant diterpenes.